Division of Allergy and Immunology, University of California and Rady Children's Hospital, San Diego, USA.
J Allergy Clin Immunol. 2010 Dec;126(6):1198-204.e4. doi: 10.1016/j.jaci.2010.08.050. Epub 2010 Nov 3.
Increased numbers of mast cells are present in the esophageal epithelium in patients with eosinophilic esophagitis (EE). However, mast cell infiltration into the esophageal lamina propria (LP) and smooth muscle (SM) and the effects of their products on SM function has not been determined.
We investigated mast cell localization and characterization in esophageal SM, the functional significance of mast cell TGF-β1 expression to contraction of human esophageal smooth muscle (HESM) cells in vitro, and the effect of topical corticosteroids on the number of tryptase-positive (MC(T)) and chymase-positive (MC(C)) mast cells in patients with EE.
MC(T)- and MC(C)-positive mast cell numbers were quantitated in the epithelium, the LP before and after topical corticosteroid therapy, and the muscularis mucosa in patients with EE and control subjects by using immunohistology. Double immunofluorescence was used to assess mast cell production of TGF-β1. The ability of TGF-β1 to influence HESM cell contractility was assessed in vitro.
In the SM in patients with EE, significantly increased numbers of MC(T)- and TGF-β1-positive cells (but only low levels of eosinophils) were detected compared with those seen in control subjects. MC(T) expressed TGF-β1, which increased the contractility of cultured primary HESM cells in vitro. Topical corticosteroid therapy in patients with EE significantly reduced epithelial MC(T) numbers but not LP tryptase-chymase-positive mast cell numbers.
MC(T) numbers, rather than eosinophil numbers, are increased in the SM in patients with EE, express TGF-β1, and increase the contractility of HESM cells in vitro. As such, mast cells localized to SM in patients with EE might modulate esophageal contractility.
嗜酸性食管炎(EE)患者的食管上皮中存在大量肥大细胞。然而,肥大细胞浸润食管固有层(LP)和平滑肌(SM)以及其产物对 SM 功能的影响尚未确定。
我们研究了 SM 中肥大细胞的定位和特征,体外研究肥大细胞 TGF-β1 表达对人食管平滑肌(HESM)细胞收缩的功能意义,以及局部皮质类固醇对 EE 患者中类胰蛋白酶阳性(MC(T))和糜蛋白酶阳性(MC(C))肥大细胞数量的影响。
通过免疫组织化学法,定量检测 EE 患者和对照受试者的上皮、经局部皮质类固醇治疗前后的 LP 和黏膜肌层中的 MC(T)和 MC(C)阳性肥大细胞数量。采用双重免疫荧光法评估肥大细胞 TGF-β1 的产生。体外评估 TGF-β1 对 HESM 细胞收缩能力的影响。
与对照受试者相比,EE 患者的 SM 中 MC(T)和 TGF-β1 阳性细胞(但仅见少量嗜酸性粒细胞)数量明显增加。MC(T)表达 TGF-β1,增加了体外培养的原代 HESM 细胞的收缩性。EE 患者的局部皮质类固醇治疗显著降低了上皮 MC(T)数量,但未降低 LP 类胰蛋白酶-糜蛋白酶阳性肥大细胞数量。
EE 患者 SM 中的 MC(T)数量而非嗜酸性粒细胞数量增加,表达 TGF-β1,并增加了体外 HESM 细胞的收缩性。因此,EE 患者 SM 中的肥大细胞可能调节食管收缩性。